Biomimetic cascade cyclizations of isoprenoid polyalkenes initiated by photoinduced electron transfer: Studies aimed at improvements and asymmetric induction

Tez Türü: Doktora

Tezin Yürütüldüğü Kurum: Kıbrıs (Kktc)

Tez Danışmanı: Huriye Icil

Tezin Onay Tarihi: 2004

Tezin Dili: İngilizce

Özet:

A methodology for the one-step synthesis of cyclic polyalkene terpenoids in low – polarity solvent, i.e. in dichloromethane via Photoinduced Electron Transfer (PET) is described. For the efficiency of such processes in low – polarity solvent, the use of the cationic electron acceptor N-methylquinoliniumhexafluorophosphate is vital. With the new conditions specified here the first direct cyclization of farnesol and geranylgeraniol to the corresponding all-trans-fused 6,6- and 6,6,6-cyclic products have been achieved. The mechanism of the termination step of cyclizations of 1,1-dinitrile substituted polyalkenes is also probed where isotope – labeling experiments showed that termination proceeds through reduction of the final radical to the corresponding anion, followed by protonation.

The effect of electron acceptor (i.e. neutral vs cationic), solvent (i.e. polar vs nonpolar) and nucleophile on the efficiency of PET cyclization of non – aromatic and aromatic polyalkene derivatives are probed. For the PET initiated cyclizations of non – aromatic isoprenoid polyalkenes, the best combination is cationic electron acceptor and polar solvent where with these conditions even sterically hindered nucleophiles can add to the generated radical cations efficiently. In the case of aromatic polyalkene cyclizations, cationic electron acceptor gives poor results regardless of solvent and nucleophile used. Mechanistically, the termination step of the cyclization process of aromatic polyalkenes is different than the non – aromatic acylic polyalkenes.

The effect on selectivity of addition and cyclization of a chiral nucleophile to radical cation generated via PET is also probed. In the case of chiral nucleophiles used here, the addition of chiral nucleophile to the cation radical generated via PET is not stereoselective except in one case where 50% diastereomeric excess has been obtained. In general, in PET, addition of chiral nucleophile for stereoselective synthesis can not be considered and applied as a general method.

As an approach to induce asymmetry and obtain enantiomerically enriched compounds via PET initiated cyclizations, a chiral Host molecule for substrate binding via Hydrogen bonds is designed. Binding studies carried out in dichloromethane using NMR titration method showed that chiral host binds to the substrate geranic acid via two Hydrogen bonds forming 1 : 1 complex. On the other hand addition of methanol disturbs this bonding interactions and reduces the complex stability significantly.

Modifications on chiral host lead to the preparation of chiral Lewis acid complexes where the utilization of later in PET lead to significant yield enhancement.